Hybrids formed by polyethylene glycol fusion of rat liver cells containing abnormal cytoplasmic aggregates of intermediate filaments, with murine hepatoma cells which show a normal distribution of intermediate filaments, will be examined in an effort to determine the type and extent of genetic control involved in maintaining the altered cytoskeletal structure. The hybrids will, furthermore, be analyzed for their ability to synthesize albumin, alpha fetoprotein and gammaglutamyltranspeptidase. We will conduct experiments in which freshly isolated rat liver cells, as well as an established normal rat liver cell line, will be incubated with diethylnitrosamine and N-methyl-N'-nitro-N-nitrosoguanine followed by the promoter 12-0-tetradecanoyl-phorbol-13 acetate. The progeny will be examined for mutagenic changes and for neoplastic transformation.